Spotlight on early-career researchers: a Neuronet interview with Anna Mallach

In this spotlight on early-career researchers interview, we speak with Anna Mallach. Anna recently joined the lab of Professor De Strooper and Dr Arancibia at the UK Dementia Research Institute at UCL to study cells in human post-mortem tissue. We asked Anna about her career, research as part of the public-private PHAGO project, as well as about challenges & opportunities in her field.


What made you decide to follow a career in science?

I really enjoy solving problems and figuring out how something worked. And for me, the brain is essentially one big problem, that we still haven’t figured out yet. There are so many things we don’t understand: how this accumulation of cells leads to consciousness, how experiences influence the brain, how damage to a specific area can lead to widespread symptoms, and so on.

I wanted to understand all of these processes better and during my undergrad, became more and more fascinated with neurodegenerative diseases and the processes leading to these various symptoms. After a Masters learning experimental techniques, I started a PhD at UCL, specifically looking at how cells interact in Alzheimer’s disease. Slightly delayed by the pandemic, I finished the PhD in the beginning of 2021 and have since then continued my research at UCL focussing on Alzheimer’s disease.


What motivates you to do science communication in addition to your lab research?

Science doesn’t exist in a vacuum. Scientists work to improve the lives of patients and are funded by the public to do so. I think it is a duty of every scientist to communicate with the public to justify what we’re doing and how it can be useful. I also just really enjoy science communication. You get to see your research through the eyes of other people, get to appreciate the overall wonder that we can even ask these questions and are sometimes also faced with some really interesting questions or approaches you haven’t considered yet.


What are you working on at the moment?

After my PhD, I changed gears a bit and switched from looking at specific cell interactions to studying how cells actually respond to Alzheimer’s disease pathology. I recently joined the lab of Professor De Strooper and Dr Arancibia at the UK Dementia Research Institute at UCL to study cells in human post-mortem tissue. That will allow us to better understand what is happening in the disease itself, meaning we can better model the disease and treat it.


What is TREM2 and why is it relevant for research on Alzheimer’s disease?

TREM2 is a protein that can sense what is going on in the environment surrounding the immune cells in the brain. Based on what it “sees”, it can tell the immune cells how to react. Interestingly, if TREM2 doesn’t work the way it should, for example when there is a mutation, patients have a much higher risk of getting Alzheimer’s disease. This means that TREM2 functioning the way it should is important and that if it doesn’t, it could encourage Alzheimer’s to develop. So understanding what TREM2 does and what functions of the immune cell it influences is really important for understanding processes underlying Alzheimer’s disease.


You recently published a scientific article as part of research, funded through the Innovative Medicines Initiative’s PHAGO project. What were your main findings?

We used human immune cells that had TREM2 mutations that were linked to Alzheimer’s disease, and we found that this seriously disrupted how the immune cells communicated with the rest of the brain. TREM2 dysfunction, meaning that the immune cells cannot sense their environment, meant that these immune cells were less supportive to the other cells in the brain. This really highlighted the importance of communication between the different cells and how that can influence how every cell behaves.


What impact do you hope your work will have in the long run?

There is a lot that scientists don’t know yet about the pathways that lead to Alzheimer’s disease. Without knowing what is going wrong in the disease, finding treatments is like shooting in the dark. Ultimately, I hope that my work will give us a better understanding of what is going wrong. Knowing that will allow us to specifically target these disease processes with treatments.

PHAGO involves many academic, industry and SME partners. What has been your experience of working on such a large public-private partnership?

I really enjoyed working within the PHAGO consortium. With so many academic and industrial partners, there was always a lively debate about results and the collaborative environment meant that I could access a wide range of different techniques.


What do you see as the key challenges & opportunities for your field?

A key challenge is the translation of findings into clinics. The animal models used for basic research do not fully recapitulate what is happening in humans and so, treatments that work well in mice may not translate well to humans. Using innovative techniques to conduct research on human cells is one chance to generate more useful, translatable data. I see that as a big opportunity to develop better models for the disease.

Selected papers:

Mallach, A., Gobom, J., Zetterberg, H., Hardy, J., Piers, T.M., Wray, S., Pocock, J.M. (2021) The influence of the R47H TREM2 variant on microglial exosome profiles. Brain Communications.

This is the preceding paper that works as a basis to the paper published in Cells.


Piers, T. M., Cosker, K., Mallach, A., Johnson, G. T., Guerreiro, R., Hardy, J., & Pocock, J. M. (2019). A locked immunometabolic switch underlies TREM2 R47H loss of function in human iPSC‐derived microglia. The FASEB Journal.

This paper establishes the model used to generate the cells, used in the Cells paper.